Project Summary/Abstract Despite widespread public health campaigns, children have become increasingly inactive, leading to public health concerns for children of industrialized nations. In addition to physical health issues (e.g., the recent obesity pandemic), physical inactivity has been related to decreased cognitive and academic performance, with a wealth of literature indicating that physical activity is positively related to brain and cognition. The significance of this proposal lies in uncovering a biomarker that links the beneficial effects of a single bout of aerobic exercise to childhood brain, cognition, and academic achievement. To date, no such explanatory mechanism has been demonstrated in the literature. Given the importance of physical activity to brain health and cognition, we propose to investigate phasic shifts in sympathetic nervous system (SNS) activity using the biomarker salivary alpha-amylase (sAA), as a potential mechanism mediating the beneficial effect of a single bout of exercise on brain, cognition, and achievement in children using a randomized crossover design. sAA is phasically increased during physical and psychosocial stress as part of the first wave of the `fight or flight' response. Stress-induced modulation of sAA has been related to alterations in prefrontally-mediated executive control functions (i.e., inhibition, working memory, cognitive flexibility) and academic achievement in children. This proposal aims to study phasic shifts in sAA following a bout of aerobic exercise, and relate such changes to measures of brain function (i.e., the P3 component of an event-related brain potential), executive control, and performance on standardized achievement tests of reading and arithmetic. In this regard, the proposed research will be the among the first to investigate the molecular underpinnings of the acute exercise-induced changes in cognition and brain in children through a combination of molecular, neuroimaging, behavioral, and academic achievement measures. Through the collection of salivary, neuroimaging, and behavioral outcomes in the proposed randomized crossover experiments, we can begin to establish the multidimensional nature of the transient effects of a single bout of exercise on the underlying molecular and neural changes that promote cognitive health and academic achievement during childhood. Findings consistent with our general hypothesis, that the SNS mediates exercise effects on brain, cognition, and achievement, has considerable implications for understanding factors that lead to maximizing physical health, neurocognitive function, and the educational experience. Such empirical support stands to benefit educational practices and current methods of learning, and provides the necessary `hard evidence' to promote the adoption of exercise during the school day to improve the cognitive health and scholastic performance of a broad range of children. Accordingly, the proposed research is not only aimed at determining a mechanism underlying the effects of a single bout of exercise on cognitive and brain health, but also at curbing the public health issue of inactivity that is decreasing the health, wellness, and academic potential of our nation's children.